Diagnostic markers for ischemia

Abstract

This invention relates to the diagnosis and monitoring of ischemia, including but not limited to myocardial and cerebral ischemia, by measuring the concentration of molecules that do not originate from the ischemic tissue but whose concentration in the blood and other fluids changes as a consequence of the ischemic state.

1. A method of identifying patients at risk of mortality at three years after an ischemic event, at risk for hemorrhage after receiving reperfusion therapy or long-term risk of mortality or arrhythmia in a non-acute patient comprising the steps of:
 measuring the level of an ischemic marker in a body fluid sample from said patient before anti-ischemic treatment, wherein the ischemic marker is unbound free fatty acid; 
 comparing the measured level of the ischemic marker from the patient to a threshold level of the ischemic marker, wherein a threshold level of unbound free fatty acid of 1.5 to 2.5 nM signifies low risk, a threshold level of unbound free fatty acid of 2.5 to 4.0 nM signifies low to medium risk, a threshold level of 4.0 to 7.5 nM unbound free fatty acid signifies medium to high risk and a threshold level of unbound free fatty acid greater than 7.5 nM signifies highest risk, wherein said threshold level is determined from measuring the ischemic marker in body fluid of an ischemic population; and 
 correlating the measured level of the ischemic marker from the patient with the threshold level, thereby identifying patients at risk of mortality at three years after an ischemic event, at risk for hemorrhage after receiving reperfusion therapy or long-term risk of mortality or arrhythmia in a non-acute patient. 
 
     
     
       2. The method of  claim 1 , wherein the anti-ischemia treatment is selected from reperfusion therapy, antithrombolytic therapy, angiogenic therapy, surgery and combinations thereof. 
     
     
       3. The method of  claim 2 , wherein the treatment is reperfusion therapy and wherein said reperfusion therapy comprises angioplasty. 
     
     
       4. The method of  claim 2 , wherein the treatment is reperfusion therapy and wherein said reperfusion therapy comprises administration of a thrombolytic agent. 
     
     
       5. The method of  claim 1 , wherein the level of unbound free fatty acid is determined in plasma or serum. 
     
     
       6. The method of  claim 1 , wherein the level of unbound free fatty acid is determined by binding to acrylodan labeled intestinal fatty acid binding protein with a substitution of Ala for Leu at position 72 (ADIFAB2). 
     
     
       7. The method of  claim 6 , wherein the binding is carried out at a temperature of 20-24° C. 
     
     
       8. The method of  claim 1 , wherein the risk of mortality is correlated with increased levels of unbound free fatty acid due to cardiovascular disease. 
     
     
       9. The method of  claim 8 , wherein the cardiovascular disease is myocardial infarction.